Re: inconsistency in ABF results for helix unfolding

Date: Wed Jan 28 2015 - 14:50:14 CST

Thank you so much for you quick reply,

Niklaus, I totally agreed that shorter end to end distance does not
necessary mean that the peptide is helica. Dihedral angles as a CV, only
have four groups of atoms available regarding one single torsion angle,
which means, I guess, 56 torsion angles need to be defined to cover all phi
and psi dihedrals in 28 peptide chain?!?! Also I am not sure what should I
considered as a reaction coordinates ? it is the same with h-bond colvar,
there are many reaction coordinates correlated together!! I have no
experience with this Colvar, so sorry if it is a naive question.

ps: I ran 50ns for 5A windows (40 - 45) still not getting results

Ajasja, I have not read that and I took a quick look, it should be a great
starting point to see if I can resolve my issue. Hopefully there are some
NAMD friendly solution in this paper.

Thank you again, and I will keep you posted if I find any solutions.


On Wed, Jan 28, 2015 at 5:05 AM, Ajasja Ljubetič <>

> Exactly, choosing the colvar(s) is crucial. Meheran, have you perhaps read Comer
> et. al <> [1], in
> particular the section "Hidden Barriers and Other Challenges to Obtaining
> Accurate Results"?
> Best regards,
> Ajasja
> 1.
> Comer, J. *et al.* The Adaptive Biasing Force Method: Everything You
> Always Wanted To Know but Were Afraid To Ask. *J. Phys. Chem. B* (2014).
> doi:10.1021/jp506633n
> On 28 January 2015 at 10:49, gmail <> wrote:
>> Hi,
>> I think that in free energy calculations, choosing a good collective
>> variable is usually more important than the method used (which more or less
>> all suffer from the same problems). Sampling is obviously the second big
>> issue.
>> It seems you used end to end distance as a collective variable, which
>> does not strike me as the best choice. The peptide could be unfolded and
>> still have a short end to end distance. On the other hand, a shorter end to
>> end distance does not mean that the peptide is helical. And a long end to
>> end distance constrains the peptide to be straight, hence largely limiting
>> the conformational space available to the unfolded peptide.
>> In that respect your test case might not be a great one, as alanine is
>> known to show a strong bias towards helical conformations. Hence in that
>> particular case the helical structure will be dominant for shorter
>> distances whereas this might not be the case for your peptide. I would
>> think about trying some other CV that would describe the end states of
>> interest better (such as H-bonds and dihedral angles or the AlphaRMSD
>> variable available in PLUMED).
>> How long were your simulations? A 24 residue peptide has a much more
>> conformational freedom than a 10 residue peptide, especially when unfolded.
>> So much larger variations in the calculated free energy should be expected
>> due to sampling issues.
>> Best,
>> Niklaus
>> Dr. Niklaus Johner
>> University of Basel
>> Klingelbergstrasse 50 / 70
>> CH - 4056 Basel
>> Tél: 076 302 12 20
>> On 28 Jan 2015, at 00:09, MEHRAN MB <> wrote:
>> Dear NAMD experts,
>> I am trying to compare free energy of forming helix structure for two
>> coils with 28 residues in length. Both are identical except, in one all GLU
>> are substituded by ALA. Indeed, I want to measure these residue
>> contribution in forming helix, and I need to calculate Free energy with
>> high precision.
>> I tried ABF method and it works great for deca-alanine in vacuum. I run
>> multiple simulations and all gave me pretty consistence results, both in
>> curve shape and final value. free-energy vs reaction-coordinates result is
>> provided. (Also when I solvate them in water I could not get good result)
>> <deca-alanine_vacuum.png>
>> However trying ABF on my 28 res polypeptide in vacuum, set boundary on
>> end-to-end distance to vary from 40A to 80A and #samples within 40000 to
>> 200,000; I have seen pretty inconsistency in free energy curve and final
>> value. Since there are few charged residues I thought it might trapped in a
>> non-equilibrium state.
>> I divided the ABF process to smaller windows. I tried first small window,
>> end-to-end distance varying from 40A to 45A and sampling from 100,000 to
>> 200,000, and I am still getting pretty inconsistent result ( from 5 to 10
>> Kcal/mol ) for this window.
>> So I believe I have enough sampling but it does not necessary mean that
>> It has been sampled in equilibrium state. So How I can make sure that I am
>> sampling in *quasi*-*equilibrium* process ?
>> Next step would be measuring this helix unfolding Free energy in solution
>> since I doubt I can say anything about the free energy in solution from
>> vacuum simulation results. (I might be wrong, )
>> any advice help to improve ABF results or suggestion about other methods
>> will be appreciated,
>> Best,
>> Mehran
>> UOttawa
>> here is simulation details:
>> 0.5 timesteps
>> rigidbond none
>> 0.1 bin width
>> 1000 fullsampling

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